OBJECTIVES: The DIrect Statin COmparison of LDL-C Values: an Evaluation of Rosuvastatin therapY (DISCOVERY)-Asia study is one of nine independently powered studies assessing the efficacy of starting doses of statins in achieving target lipid levels in different countries worldwide. DISCOVERY-Asia was a 12-week, randomised, open-label, parallel-group study conducted in China, Hong Kong, Korea, Malaysia, Taiwan, and Thailand.
RESULTS: A total of 1482 adults with primary hypercholesterolaemia and high cardiovascular risk (> 20%/10 years, type 2 diabetes, or a history of coronary heart disease) were randomised in a 2 : 1 ratio to receive rosuvastatin 10 mg once daily (o.d.) or atorvastatin 10 mg o.d. The percentage of patients achieving the 1998 European Joint Task Force low-density lipoprotein cholesterol (LDL-C) goal of < 3.0 mmol/L at 12 weeks was significantly higher in the rosuvastatin group (n = 950) compared with the atorvastatin group (n = 471) (79.5 vs. 69.4%, respectively; p < 0.0001). Similar results were observed for 1998 European goals for total cholesterol (TC), and the 2003 European goals for LDL-C and TC. LDL-C and TC levels were reduced significantly more with rosuvastatin compared with atorvastatin. Both drugs were well-tolerated and the incidence and type of adverse events were similar in each group.
TRIALS REGISTRATION: The trial registry summary is available at http://www.clinicaltrials.gov/; ClinicalTrials.gov Identifier: NCT00241488
CONCLUSIONS: This 12-week study showed that the starting dose of rosuvastatin 10 mg o.d. was significantly more effective than the starting dose of natorvastatin 10 mg o.d. at enabling patients with primary hypercholesterolaemia to achieve European goals for LDL-C and TC in a largely Asian population in real-life clinical practice. The safety profile of rosuvastatin 10 mg is similar to that of atorvastatin 10 mg in the Asian population studied here, and is consistent with the known safety profile of rosuvastatin in the white population.
MATERIALS AND METHODS: This was an investigator-initiated, single-center, randomized, controlled, clinical trial in patients with T2DM and DKD, comparing 12-weeks of low carbohydrate diet (<20g daily intake) versus standard low protein (0.8g/kg/day) and low salt diet. Patients in the VLCBD group underwent 2-weekly monitoring including their 3-day food diaries. In addition, Dual-energy x-ray absorptiometry (DEXA) was performed to estimate body fat percentages.
RESULTS: The study population (n = 30) had a median age of 57 years old and a BMI of 30.68kg/m2. Both groups showed similar total calorie intake, i.e. 739.33 (IQR288.48) vs 789.92 (IQR522.4) kcal, by the end of the study. The VLCBD group showed significantly lower daily carbohydrate intake 27 (IQR25) g vs 89.33 (IQR77.4) g, p<0.001, significantly higher protein intake per day 44.08 (IQR21.98) g vs 29.63 (IQR16.35) g, p<0.05 and no difference in in daily fat intake. Both groups showed no worsening of serum creatinine at study end, with consistent declines in HbA1c (1.3(1.1) vs 0.7(1.25) %) and fasting blood glucose (1.5(3.37) vs 1.3(5.7) mmol/L). The VLCBD group showed significant reductions in total daily insulin dose (39(22) vs 0 IU, p<0.001), increased LDL-C and HDL-C, decline in IL-6 levels; with contrasting results in the control group. This was associated with significant weight reduction (-4.0(3.9) vs 0.2(4.2) kg, p = <0.001) and improvements in body fat percentages. WC was significantly reduced in the VLCBD group, even after adjustments to age, HbA1c, weight and creatinine changes. Both dietary interventions were well received with no reported adverse events.
CONCLUSION: This study demonstrated that dietary intervention of very low carbohydrate diet in patients with underlying diabetic kidney disease was safe and associated with significant improvements in glycemic control, anthropometric measurements including weight, abdominal adiposity and IL-6. Renal outcomes remained unchanged. These findings would strengthen the importance of this dietary intervention as part of the management of patients with diabetic kidney disease.
METHODS: Using a 2-by-2-by-2 factorial design, we randomly assigned participants without cardiovascular disease who had an elevated INTERHEART Risk Score to receive a polypill (containing 40 mg of simvastatin, 100 mg of atenolol, 25 mg of hydrochlorothiazide, and 10 mg of ramipril) or placebo daily, aspirin (75 mg) or placebo daily, and vitamin D or placebo monthly. We report here the outcomes for the polypill alone as compared with matching placebo, for aspirin alone as compared with matching placebo, and for the polypill plus aspirin as compared with double placebo. For the polypill-alone and polypill-plus-aspirin comparisons, the primary outcome was death from cardiovascular causes, myocardial infarction, stroke, resuscitated cardiac arrest, heart failure, or revascularization. For the aspirin comparison, the primary outcome was death from cardiovascular causes, myocardial infarction, or stroke. Safety was also assessed.
RESULTS: A total of 5713 participants underwent randomization, and the mean follow-up was 4.6 years. The low-density lipoprotein cholesterol level was lower by approximately 19 mg per deciliter and systolic blood pressure was lower by approximately 5.8 mm Hg with the polypill and with combination therapy than with placebo. The primary outcome for the polypill comparison occurred in 126 participants (4.4%) in the polypill group and in 157 (5.5%) in the placebo group (hazard ratio, 0.79; 95% confidence interval [CI], 0.63 to 1.00). The primary outcome for the aspirin comparison occurred in 116 participants (4.1%) in the aspirin group and in 134 (4.7%) in the placebo group (hazard ratio, 0.86; 95% CI, 0.67 to 1.10). The primary outcome for the polypill-plus-aspirin comparison occurred in 59 participants (4.1%) in the combined-treatment group and in 83 (5.8%) in the double-placebo group (hazard ratio, 0.69; 95% CI, 0.50 to 0.97). The incidence of hypotension or dizziness was higher in groups that received the polypill than in their respective placebo groups.
CONCLUSIONS: Combined treatment with a polypill plus aspirin led to a lower incidence of cardiovascular events than did placebo among participants without cardiovascular disease who were at intermediate cardiovascular risk. (Funded by the Wellcome Trust and others; TIPS-3 ClinicalTrials.gov number, NCT01646437.).
OBJECTIVES: (1) To compare the concentrations of biomarkers of inflammation, endothelial activation and oxidative stress in subjects with low HDL-c compared to normal HDL-c; (2) To examine the association and correlation between HDL-c and these biomarkers and (3) To determine whether HDL-c is an independent predictor of these biomarkers.
METHODS: 422 subjects (mean age±SD = 43.2±11.9 years) of whom 207 had low HDL-c concentrations (HDL-c <1.0 mmol/L and <1.3 mmol/L for males and females respectively) and 215 normal controls (HDL-c ≥1.0 and ≥1.3 mmol/L for males and females respectively) were recruited in this study. The groups were matched for age, gender, ethnicity, smoking status, diabetes mellitus and hypertension. Fasting blood samples were collected for analysis of biomarkers of inflammation [high-sensitivity C-reactive protein (hsCRP) and Interleukin-6 (IL-6)], endothelial activation [soluble Vascular Cell Adhesion Molecule-1 (sVCAM-1), soluble Intercellular Adhesion Molecule-1 (sICAM-1) and E-selectin)] and oxidative stress [F2-Isoprostanes, oxidized Low Density Lipoprotein (ox-LDL) and Malondialdehyde (MDA)].
RESULTS: Subjects with low HDL-c had greater concentrations of inflammation, endothelial activation and oxidative stress biomarkers compared to controls. There were negative correlations between HDL-c concentration and biomarkers of inflammation (IL-6, p = 0.02), endothelial activation (sVCAM-1 and E-selectin, p = 0.029 and 0.002, respectively), and oxidative stress (MDA and F2-isoprostane, p = 0.036 and <0.0001, respectively). Multiple linear regression analysis showed HDL-c as an independent predictor of IL-6 (p = 0.02) and sVCAM-1 (p<0.03) after correcting for various confounding factors.
CONCLUSION: Low serum HDL-c concentration is strongly correlated with enhanced status of inflammation, endothelial activation and oxidative stress. It is also an independent predictor for enhanced inflammation and endothelial activation, which are pivotal in the pathogenesis of atherosclerosis and atherosclerosis-related complications.
OBJECTIVES: The authors sought to assess the LDL-C efficacy of rosuvastatin versus placebo in HoFH children, and the relationship with underlying genetic mutations.
METHODS: This was a randomized, double-blind, 12-week, crossover study of rosuvastatin 20 mg versus placebo, followed by 12 weeks of open-label rosuvastatin. Patients discontinued all lipid-lowering treatment except ezetimibe and/or apheresis. Clinical and laboratory assessments were performed every 6 weeks. The relationship between LDL-C response and genetic mutations was assessed by adding children and adults from a prior HoFH rosuvastatin trial.
RESULTS: Twenty patients were screened, 14 randomized, and 13 completed the study. The mean age was 10.9 years; 8 patients were on ezetimibe and 7 on apheresis. Mean LDL-C was 481 mg/dl (range: 229 to 742 mg/dl) on placebo and 396 mg/dl (range: 130 to 700 mg/dl) on rosuvastatin, producing a mean 85.4 mg/dl (22.3%) difference (p = 0.005). Efficacy was similar regardless of age or use of ezetimibe or apheresis, and was maintained for 12 weeks. Adverse events were few and not serious. Patients with 2 defective versus 2 negative LDL receptor mutations had mean LDL-C reductions of 23.5% (p = 0.0044) and 14% (p = 0.038), respectively.
CONCLUSIONS: This first-ever pediatric HoFH statin trial demonstrated safe and effective LDL-C reduction with rosuvastatin 20 mg alone or added to ezetimibe and/or apheresis. The LDL-C response in children and adults was related to underlying genetic mutations. (A Study to Evaluate the Efficacy and Safety of Rosuvastatin in Children and Adolescents With Homozygous Familial Hypercholesterolemia [HYDRA]; NCT02226198).
AIM OF THE STUDY: To evaluate kratom's effects towards hematological and clinical-chemistry parameters among regular kratom users in Malaysia.
METHODS: A total of 77 subjects (n=58 regular kratom users, and n=19 healthy controls) participated in this cross-sectional study. All the surveys were conducted through face-to-face interview to elicit subject's socio-demographic characteristics and kratom use history. A full-blood test was also administered. Laboratory analysis was conducted using GC-MS to determine mitragynine content in the acquired kratom samples in order to relate mitragynine consumption with possible alterations in the blood parameters of kratom users.
RESULTS: Findings showed that there were no significant differences in the hematological and clinical-chemistry parameters of traditional kratom users and healthy controls, except for HDL and LDL cholesterol values; these were found to be above the normal reference range for the former. Similarly, long-term kratom consumption (>5 years), and quantity of daily kratom use (≥3 ½ glasses; mitragynine content 76.3-114.8mg) did not appear to alter the hematological and biochemical parameters of kratom users.
CONCLUSION: These data suggest that even long-term and heavy kratom consumption did not significantly alter the hematological and clinical-chemistry parameters of kratom users in a traditional setting.
AIM OF THE STUDY: This study aims to investigate the anti-obesity and lipid lowering effects of ethanolic extract of C. cauliflora leaves and its major compound (vitexin) in C57BL/6 obese mice induced by high-fat diet (HFD), as well as to further identify the molecular mechanism underlying this action.
METHODS AND MATERIAL: Male C57BL/6 mice were fed with HFD (60% fat) for 16 weeks to become obese. The treatment started during the last 8 weeks of HFD feeding and the obese mice were treated with C. cauliflora leaf extract at 200 and 400 mg/kg/day, orlistat (10 mg/kg) and vitexin (10 mg/kg).
RESULTS: The oral administration of C. cauliflora (400 and 200 mg/kg) and vitexin significantly reduced body weight, adipose tissue and liver weight and lipid accumulation in the liver compared to control HFD group. Both doses of C. cauliflora also significantly (P ≤ 0.05) decreased serum triglyceride, LDL, lipase, IL-6, peptide YY, resistin levels, hyperglycemia, hyperinsulinemia, and hyperleptinemia compared to the control HFD group. Moreover, C. cauliflora significantly up-regulated the expression of adiponectin, Glut4, Mtor, IRS-1 and InsR genes, and significantly decreased the expression of Lepr in white adipose tissue. Furthermore, C. cauliflora significantly up-regulated the expression of hypothalamus Glut4, Mtor and NF-kB genes. GC-MS analysis of C. cauliflora leaves detected the presence of phytol, vitamin E and β-sitosterol. Besides, the phytochemical evaluation of C. cauliflora leaves showed the presence of flavonoid, saponin and phenolic compounds.
CONCLUSION: This study shows interesting outcomes of C. cauliflora against HFD-induced obesity and associated metabolic abnormalities. Therefore, the C. cauliflora extract could be a potentially effective agent for obesity management and its related metabolic disorders such as insulin resistance and hyperlipidemia.